Recent progress on an endogenous digitalislike factor in hypertension

Evidence exists that demonstrates the relationship between a natriuretic factor, or Na+, K+-ATPase inhibitor, and volume expansion in man. Patients having extracellular volume expansion have been studied for the effect of their plasma on erythrocyte [3H]ouabain binding. High levels of ouabainlike activity were found in plasma from acromegalic patients and patients with chronic renal failure. High levels were also observed in some hypertensive patients. A partial purification of such a compound was performed from the urine of hypertensive patients. The various steps of purification achieved a 400,000-fold purified compound of apparent homogeneity. The inhibitor was extracted from 140 liters of urine of 21 donors (hypertensive patients and normotensive offspring of hypertensive patients). The purification steps included flash chromatography, anionic exchange, and reversed-phase HPLC on RP 18, diphenyl and phenyl packings. Nuclear magnetic resonance and mass spectrometry indicated a nonpeptidic compound, which was possibly a steroid with a low molecular mass (less than 500 daltons).